There is a need to develop a method which could be used in toxicological studies using rodents to detect the development of pneumotoxicity induced by chemicals. The ideal method should be non-invasive, easy to perform, yield highly reproducible results, applicable repeatedly on the same animal and sensitive enough to detect early toxic changes. We are proposing that measurement of ventilatory response to CO2 in rats and guinea-pigs can be used to assess the development of pneumotoxicity which would be indicated by a lower than normal ventilatory response. A whole body plethysmograph will be used to measure the response to CO2 before and after exposure to various toxicants. The method will require no anesthesia and no restraint of the animals. A second method is also proposed to measure flow resistive work in guinea-pigs and rats during normal breathing as well as during increased tidal volume. It is a non-invasive method which can also be used in detecting the effect of pneumotoxicants. Both methods could be used repeatedly, they are ideal in long-term toxicity studies to follow the development of pneumotoxicity during exposure to air pollutants or ingestion of any chemicals. To study the applicability of these methods three pulmonary toxicants were selected. The animals will be exposed to aerosols of sulfuric acid or to nitrogen dioxide or will receive paraquat given intraperitoneally. All three will be used at levels producing various degrees of pulmonary toxicity to evaluate the detection capability of the methods we are proposing.